The dose-adjusted EPOCH regimen was developed based on in vitro and pharmacodynamic principals to help overcome drug resistance. In this regimen, doxorubicin, vincristine, and etoposide are administered as a 96-hour continuous infusion, and cyclophosphamide and prednisone are administered on a bolus schedule. The rationale for the administration schedule derived from the laboratory observation that human tumor cell lines, including those with a multi-drug resistance phenotype, are more sensitive to cytotoxic natural products given for prolonged periods at low concentrations than to the same agents given for brief periods at higher concentrations. Multiple phase II studies suggests it is superior to R-CHOP, possibly due to overcoming tumor proliferation and increasing cell tumor cell kill. If superior to R-CHOP, it will increase the cure of DLBCL. This study showed similar outcome in both arms. However, high risk patients showed an improved outcome with DA-EPOCH-R. Currently we are analyzing the molecular characteristics of the samples.